The metabolism of carbon 14 labeled methoxsalen by the dog

Single doses of 14C-methoxsalen (5 mg/kg, 9-methoxy-7H-furo[3,2-g] [1] benzopyran-7-one) a photochemotherapeutic agent. For the treatment of psoriasis were administered i.v. to 3 dogs. Almost as much administered radioactivity was excreted in the feces as in the urine suggesting that biliary secretion of metabolites was an important route of excretion. 14C-Methoxsalen disappeared rapidly from plasma although plasma levels of radioactivity persisted for 5 wk after drug administration. Apparently the persistent plasma radioactivity was due to a metabolite bound to plasma protein. Urinary metabolites (4) were isolated. Three of the metabolites were due to furan ring opening: these are 7-hydroxy-8-methoxy-2-oxo-2H-1-benzopyran-6-acetic acid (A), .alpha.,7-dihydroxy-8-methoxy-2-oxo-2H-1-benzopyran-6-acetic acid (B) and an unknown conjugate of A at the 7-hydroxy position. The 4th metabolite formed by opening of the pyrone ring is an unknown conjugate of (Z)-3-(6-hydroxy-7-methoxybenzofuran-5-yl)-2-propenoic acid.